Osteoidosis leads to altered differentiation and function of osteoclasts

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone

Sex differences in the morphological failure patterns following hip resurfacing arthroplasty

<p>Abstract</p> <p>Background</p> <p>Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty.</p> <p>Methods</p> <p>Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis.</p> <p>Results</p> <p>Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, <it>P </it>for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, <it>P </it>for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, <it>P </it>for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, <it>P </it>for difference = 0.03).</p> <p>Conclusions</p> <p>Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.</p

European multidisciplinary consensus statement on the use and monitoring of metal-on-metal bearings for total hip replacement and hip resurfacing.

Summary Introduction There is an ongoing debate about the optimal use of metal-on-metal (MoM) bearings in total hip replacement, since there are uncertainties about local and systemic adverse effects due to wear and corrosion of these bearings. Despite various national recommendations, efforts to achieve international harmonization of specific evidence-based recommendations for best practice are still lacking. Hypothesis An international consensus study group should be able to develop recommendations on the use and monitoring of MoM bearings, preferably at the European level, through a multidisciplinary approach, by integrating the perspectives of various stakeholders. Materials and methods Twenty-one experts representing three stakeholder groups and eight countries participated in this European consensus study, which consisted of a consensus meeting, subsequent structured discussion, and consensus voting. Results The current statement defines first of all benefits, local and systemic risks, as well as uncertain issues related to MoM bearings. Safety assessment after implantation of MoM comprises all patients. A closer follow-up is recommended for large head MoM (≥ 36 mm) and resurfacing. In these implants basic follow-up should consist of x-rays and metal ion measurement of cobalt in whole blood, performed with GF-AAS or ICP-MS. Clinical and/or radiographic abnormality as well as elevated ion levels needs additional imaging (ultrasound, CT-scan and/or MARS-MRI). Cobalt values less than 2 μg/L are probably devoid of clinical concern, the threshold value for clinical concern is expected to be within the range of 2–7 μg/L. Discussion This is the first multinational, interdisciplinary, and multiprofessional approach for developing a recommendation for the use and monitoring of MoM bearings in total hip replacement. The current recommendations are in partial agreement with previous statements regarding the extent of follow-up and imaging techniques. They however differ from previous communications regarding measurement of metal ions and especially the investigated medium, technique, and eventual threshold levels. Level of evidence Level V, expert opinion/agreement conference

A new short uncemented, proximally fixed anatomic femoral implant with a prominent lateral flare: design rationals and study design of an international clinical trial

<p>Abstract</p> <p>Background</p> <p>Anatomic short femoral prostheses with a prominent lateral flare have the potential to reduce stress-shielding in the femur through a more physiological stress distribution to the proximal femur. We present the design rationale of a new short uncemented, proximally fixed anatomic femoral implant and the study design of a prospective multi-centre trial to collect long-term patient outcome and radiographic follow up data.</p> <p>Methods</p> <p>A prospective surveillance study (trial registry NCT00208555) in four European centres (UK, Italy, Spain and Germany) with a follow up period of 15 years will be executed. The recruitment target is 200 subjects, patients between the ages of 18 and 70 admitted for primary cementless unilateral THA will be included. The primary objective is to evaluate the five-year survivorship of the new cementless short stem. The secondary objectives of this investigation are to evaluate the long term survivorship and the clinical performance of the implant, the impact on the subjects health related Quality of Life and the affect of the prosthesis on bone mineral density. Peri- and postoperative complications will be registered. Clinical and radiographic evaluation of prosthesis positioning will be done post-operatively and at 3, 6, 12, 24, 60, 120 and 180 months follow up.</p> <p>Discussion</p> <p>Shortening of the distal stem can maximise bone and soft tissue conservation. New stem types have been designed to improve the limitations of traditional implants in primary THA. A new, uncemented femoral short stem is introduced in this paper. A long-term follow up study has been designed to verify stable fixation and to research into the clinical outcome. The results of this trial will be presented as soon as they become available.</p

Influence of application parameters of ultrasonic-assisted bone instruments on the tear force of a substitute material for spinal dura mater

An ultrasonic-assisted bone instrument can be used for the dissection of bone in spinal surgery. During surgery, the tip of such a bone instrument can touch spinal dura mater. Especially during critical re-operations, high forces can be unintentionally applied on spinal dura mater. To prevent dural tears, the influence of application parameters on the tear force shall be analyzed. Collagen foil is used as a substitute material for spinal dura mater because of its similar mechanical properties and structure. Sponge cloth is placed below collagen foil to imitate cerebrospinal fluid and nerve tissue. A 3-axis CNC-machine is used to automate the movement of the bone instrument. In a full factorial experiment the influence of amplitude, shape of movement and velocity of movement on the tear force is analyzed. Amplitude has the strongest effect because of the increase in input energy. Velocity also has a significant influence, probably because of the strain rate increasing with velocity. Thus, a surgeon should mainly reduce the amplitude and furthermore the velocity of movement to generate higher safety in critical areas

The influence of hip revision stem spline design on the torsional stability in the presence of major proximal bone defects.

BackgroundDespite the success of primary total hip arthroplasty, the number of revisions remains high. Infection, aseptic loosening, periprosthetic fractures and dislocations are the leading causes of hip revision. Current revision stem designs feature a tapered body with circumferential placed longitudinal thin metal splines that cut into the femoral cortex of the diaphysis to provide axial and rotational stability. Modifications to the spline design may help improve primary stability in various bone qualities. The purpose of this study was to evaluate whether the rotational stability of a revision hip stem can be improved by an additional set of less prominent, wider splines in addition to the existing set of splines. It is hypothesized that the additional splines will result in greater cortical contact, thereby improving torsional strength.Methods and findingsThe ultimate torsional strength of an established modular revision stem (Reclaim®, DePuy Synthes) was compared to a Prototype stem design with two sets of splines, differing in prominence by 0.25 mm. Five pairs of fresh-frozen human femurs (n = 10) were harvested and an extended trochanteric osteotomy was performed to obtain common bone defects in revision. Stems were implanted using successive droptower impacts to omit variability caused by mallet blows. The applied energy was increased from 2 J in 1 J increments until the planned implantation depth was reached or seating was less than 0.5 mm at 5 J impact. The ultimate torsional strength of the bone-to-implant interface was determined immediately after implantation. Image superposition was used to analyze and quantify the contact situation between bone and implant within the femoral canal. Cortical contact was larger for the Prototype design with the additional set of splines compared to the Reclaim stem (p = 0.046), associated with a higher torsional stability (35.2 ± 6.0 Nm vs. 28.2 ± 3.5 Nm, p = 0.039).ConclusionsA second set of splines with reduced prominence could be shown to improve primary stability of a revision stem in the femoral diaphysis in the presence of significant proximal bone loss. The beneficial effect of varying spline size and number has the potential to further improve the longevity of revision hip stems